Chronic di-n-butyl phthalate exposure in rats reduces fertility and alters ovarian function during pregnancy in female Long Evans hooded rats.

Testis function in fetal and peripubertal male rats is disrupted by subchronic exposure to phthalate esters (PEs). In contrast to the male rat, it is generally held that reproduction in female rats is much less sensitive to phthalate-induced disruption. However, the current study demonstrates that oral administration of dibutyl phthalate (DBP) to female Long Evans (LE) hooded rats from weaning, through puberty, mating, and gestation disrupts pregnancy maintenance at dose levels similar to those that affect testis function in male rats. Administration of 500 and 1000 mg DBP/kg/day, but not 250 mg DBP/kg/day, to female LE rats induced midpregnancy abortions. The percentage of females delivering live pups was reduced by more than 50% at 500 mg/kg/day and by 90% at 1000 mg/kg/day in the absence of overt toxicity, whereas the ages at vaginal opening and first estrus, estrous cyclicity, and mating indices (N mated/N paired or N pregnant/N mated) were not significantly affected. On gestational day 13, prior to the stage when litters were being aborted, ex vivo ovarian hormone production was significantly decreased by in vivo DBP treatment at 500 and 1000 mg/kg/day. These results should be considered when evaluating mechanisms of reproductive toxicity for the PE because it is likely that these reproductive alterations in the female rat arise via a mode of action similar to that operative in male rats.     

Effects of in vitro exposure to butylparaben and di‐(2 ethylhexyl) phthalate,alone or in combination,on ovarian function

Parabens and phthalates are commercial chemicals widely used in the manufacture of industrial and consumer products frequently found as contaminants in biological fluids. We evaluated the effects of di‐(2‐ethylhexyl) phthalate (DEHP) (ranging from 10^–9 to 10^–7 m [1–100 nm ; 0.39–39 ng ml^–1]) and butylparaben (BP) (ranging from 10^–8 to 10^–5 m [10 nm– 10 μm ; 1.9 ng ml^–1 to 1.9 μg ml^–1]), alone and in combination, on isolated mouse preantral follicle and human granulosa cell (hGC) cultures to study direct effects on follicle growth and ovarian steroidogenesis. Our results revealed that, in follicle culture, DEHP and BP attenuate estradiol output but only when present together. DEHP decreases progesterone concentrations in the spent media of hGC cultures, an effect that was attenuated when BP was added together with DEHP. Although changes in steroidogenesis were observed, no effects on follicular development or survival were noted in the culture systems. We suggest that BP and DEHP act with additive effect to decrease estradiol production whereas at later stages of follicle development BP blocks the effect of DEHP in hGCs resulting in decreased progesterone output. Taken together our results suggest that DEHP and BP adversely affect steroidogenesis from the preantral stage onward and the effects of these chemicals are both stage‐dependent and modified by co‐exposure. Copyright © 2016 John Wiley & Sons, Ltd.     

Effects of the serotonin antagonist amesergide on reproduction in female rats

Amesergide, a serotonin (5-HT₂) antagonist intended to treat depression, was administered orally to female CD rats (20/group) at doses of 0, 3, 10, or 30 mg/kg to evaluate effects of mating, fertility, litter size, live birth index (100 × total liveborn progeny/litter size), progeny survival, and weight gain of each litter. The treatment period extended from two weeks prior to mating through postpartum day 21 to cover possible effects of estrons cycle, mating, gestation, and postpartum events. Twenty additional female rats were given 30 mg/kg through gestation day 18, after which they received the acacia vehicle (recovery group). All females were allowed to deliver naturally and rear their progeny. On postpartum day 8, progeny in the control, 30 mg/kg and 30 mg/kg recovery groups were removed from dams for 4 h. Progeny were weighed as litters, returned to the dams for a 1-h nursing period, and then weighed again to provide an indication of milk intake. Mating and fertility, using the present study design, were not affected by treatment with amesergide. No effects were observed on litter size, live birth index, or progeny survival. In contrast, treatment with amesergide throughout gestation and lactation produced a significant dose-related depression in progeny body weight gains. However, when treatment was discontinued after day 18 of gestation (30 mg/kg recovery group), progeny body weight gains did not differ from those of the control group. When weight gain of progeny following 1 h of nursing on postpartum day 8 was examined, the offspring of the 30 mg/kg group in which treatment was continued through lactation, exhibited a significantly lower weight gain than did those from controls or the 30 mg/kg recovery group. This difference occurred in the absence of an observable change in nursing behavior amoung treatment groups. In conclusion, treatment of maternal animals with amesergide produced a reduction in progeny body weight gains. This effect was only apparent when treatment of the females continued through lactation and appeared to be due, at least in part, to a reduction in milk consumption by the progeny suggesting an alteration in milk production of the females.     

Cadmium impairment of reproduction in the female wall lizard Podarcis sicula

The exposure to environmental toxicants such cadmium (Cd) is an important research area in wildlife protection. In this study, the effect of Cd oral administration on the ovarian structure and function and on reproductive performance of the Italian wall lizard Podarcis sicula was studied. In vivo, adult female lizards were randomly assigned to three groups. Cd was given with food in single dose and in multiple doses 3 days/week for 4 weeks at dose of 1.0 μg/g body weight. Following euthanasia, the ovaries were removed and analyzed for morpho‐functional changes. Results demonstrated that Cd increases prefollicular germ cells number; the evaluation of the number of follicles detects significantly higher number of atretic growing follicles, whereas primary follicles remain unchanged with respect to controls. After Cd treatments, follicles are deformed by the presence of large protrusions and a general dysregulation in the follicle organization is observed. The zona pellucida is also affected. Cd causes alteration in sugar metabolism and in metallothionein gene expression. Finally, Cd administration significantly reduces clutch size and dramatically increases embryo mortality. In conclusion, data here described show that Cd induces morpho‐functional alterations in lizard follicles and indicates that these are responsible for a significant impairment of oogenesis. The effects of the dose are time independent, persisting essentially unchanged regardless of single or multiple administration, so it can be concluded that even occasional, sublethal Cd contamination may significantly impair reproductive performance in these animals. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 553–562, 2013.     

Prenatal exposure to an environmentally relevant phthalate mixture accelerates biomarkers of reproductive aging in a multiple and transgenerational manner in female mice

Phthalates are known endocrine-disrupting chemicals that are found in many consumer products. Our laboratory previously developed a relevant phthalate mixture consisting of six phthalates and found that it disrupted female fertility in mice. However, it is unknown if prenatal exposure to phthalate mixtures can accelerate reproductive aging and if this occurs in multiple generations. Thus, we tested the hypothesis that prenatal exposure to a mixture of phthalates accelerates biomarkers of reproductive aging in multiple generations of female mice. Pregnant CD-1 mice were orally dosed with vehicle control or a phthalate mixture (20 μg/kg/day-500 mg/kg/day) daily from gestational day 10 to birth. Adult F1 females born to these dams were used to create the F2 and F3 generations by mating them with unexposed males. At 13 months, estrous cyclicity was monitored and ovaries and sera were collected for analysis. In the F1 generation, the mixture decreased testosterone and inhibin B levels, but increased follicle-stimulating hormone and luteinizing hormone levels compared to control. In the F2 generation, the phthalate mixture decreased the percent of antral follicles and testosterone hormone levels compared to control. In the F3 generation, prenatal exposure to the phthalate mixture increased ovarian weight, increased the time in metestrus/diestrus, altered follicle numbers, and decreased the levels of luteinizing hormone compared to control. Collectively, these data suggest that prenatal exposure to a phthalate mixture may accelerate several biomarkers of reproductive aging in a multi- and transgenerational manner in female mice.     

Effects of oral exposure to trichloroethylene on female reproductive function

The present study was conducted to determine if subchronic oral exposure to trichloroethylene (TCE) influenced female reproductive performance, and if TCE or major metabolites trichloroacetic acid (TCA) and trichloroethanol (TCOH) preferentially accumulated in female reproductive organs or neonatal tissues. Female Long-Evans hooded rats were exposed to vehicle (corn-oil), 10, 100 or 1000 mg/kg/day by gavage for 2 weeks before mating and throughout mating to day 21 of pregnancy. Gas chromatography analysis of tissues from females at the end of premating exposure indicated that TCE levels were uniformly high in fat, adrenals and ovaries across treatment groups, while uterine tissue had relatively high levels of TCA. Female fertility, however, was not influenced in any treatment group. In the 1000 mg/kg/day group, 5 out of 23 females died and weight gain was significantly depressed throughout the treatment period. Neonatal survival was significantly depressed in this group alone, with the majority of deaths occurring among female offspring at the time of birth. TCA levels in blood, liver, and milk contents of the stomach in female but not male neonates increased across treatment groups. These results indicate that oral exposure to TCE at levels below those causing limiting maternal toxicity had no influence on pregnancy outcome, and that the accumulation of TCE and TCA in ovaries, adrenals and uteri had no influence on mating success.     

Effects of di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-ovarian axis in adult female rats

Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is widely present in the environment and some products with phthalate plasticizer. It has become a serious problem in recent years. The effect of DEHP on female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on hypothalamus-pituitary-ovarian axis in adult female rats. Compared with control rats, the DEHP-treated rats showed: (1) lower body weight; (2) lower organ coefficient of ovary; (3) higher GnRH level in the hypothalamus; (4) higher mRNA and protein levels of GnRHR in the pituitary; and (5) lower serum sex hormone levels. Our data reveal that DEHP exposure may lead to the disruption of estrogen biosynthesis pathways in female rats and imbalance of hypothalamus-pituitary-ovarian axis. DEHP may impose negative influence on the development and function of the reproductive system in female rats.     

Late-life consequences of short-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate during adulthood in female mice

Di(2-ethylhexyl) phthalate (DEHP) is a known endocrine disruptor and diisononyl phthalate (DiNP) is a common DEHP replacement chemical. However, little is known about late-life consequences due to DEHP or DiNP exposure during adulthood. Thus, this study tested the hypothesis that adult exposure to DEHP or DiNP affects female reproductive parameters during late-life in female mice. Female CD-1 mice (age 39–40 days) were dosed with either vehicle control, DEHP (20 μg/kg/day–200 mg/kg/day), or DiNP (20 μg/kg/day–200 mg/kg/day) for 10 days and breeding trials were conducted at 12 and 15 months post-dosing. Further, ovaries and sera were collected at 12, 15, and 18 months post-dosing. DEHP and DiNP disrupted estrous cyclicity, increased pregnancy loss, decreased fertility, altered the sex ratio of pups, altered ovarian follicle populations, and disrupted hormone levels. Collectively, these data show that short-term exposure to DEHP or DiNP during adulthood has long-term consequences in late-life.     

Effects of acute and chronic exposure to cobalt on male reproduction in mice

Chronic exposure of male mice to cobaltous chloride dramatically affected their reproductive potential, while acute administration had minimal effects. Acute exposure, followed by evaluation weekly over a 7-week period, revealed no significant changes in epididymal sperm concentration or testicular weight. However, small but significant decreases in fertility at weeks 2 and 3 of the study were observed. Sperm motility was depressed only during the first week of the study. In chronic studies, cobalt affected fertility in a time- and dose-dependent manner. There was a decrease in testicular weight, epididymal sperm concentration, and fertility. Sperm motility was also depressed. Serum testosterone levels were dramatically increased in cobalt treated animals, while FSH and LH serum levels were normal. It appears that cobalt is directly or indirectly interfering with spermatogenesis and with local regulatory mechanisms in testosterone synthesis.     

In utero exposure to the endocrine disruptor di(2-ethylhexyl) phthalate targets ovarian theca cells and steroidogenesis in the adult female rat

Di-2-ethylhexyl phthalate (DEHP) is an endocrine disruptor used in industry as an additive to polyvinyl chloride-based products. Pregnant dams were gavaged with oil, 1, 20, 50, or 300 mg of DEHP/kg/day from gestational day 14 until birth in order to characterize the effects of DEHP in the adult female offspring. In utero exposure to DEHP resulted in reduced estrogen levels at proestrus. Theca cell layer thickness was decreased starting at 50 mg DEHP/kg/day dose. Follicle-stimulating hormone levels were significantly increased at proestrus and estrus. F1 reproduction using a known breeder was not affected. F3 generation showed a decreased pregnancy rate and weight, and increased litter size in the animals exposed to 20 mg DEHP/kg/day. The data presented herein suggest that in utero exposure to DEHP targets the theca cell layer and decreases the estrus cycle steroid surge, but despite these effects, does not cause infertility.     

Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague-Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl) phthalate

The aim of the present study was to determine the ovotoxicity of female Sprague-Dawley (SD) rats exposed to benzo[a]pyrene (B[a]P) and di-(2-ethylhexyl) phthalate (DEHP), either alone or in combination; the molecular mechanism and the combined effects were also evaluated. Female rats were given intragastric administration of control (corn oil), B[a]P (5 and 10mg/kg), DEHP (300 and 600 mg/kg) and B[a]P+DEHP (at 5mg/kg and 300 mg/kg respectively, or at 10mg/kg and 600 mg/kg respectively) on alternate days for 60 days. Relative ovary weight, estrous cycle, 17β-estradiol blood level, ovarian follicle populations, granulosa cell apoptosis, and gene and protein expression of P450Arom and PPAR were investigated. Our study demonstrated that the combination of B[a]P and DEHP exerts ovotoxicity in female rats and suppression of sex hormone secretion and homeostasis, which is associated with prolonged estrous cycles, decreases in ovarian follicle populations and granulosa cell apoptosis involving a PPAR-mediated signaling pathway of action of the two chemicals. In addition, based on qualitative assessment of the combined toxicity, no interaction effects were observed following combined B[a]P and DEHP administration.     

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression.     

卵泡刺激素受体基因多态性对女性卵巢功能影响的研究进展

卵泡刺激素(FSH)是人类重要的生殖激素,被广泛应用于体外受精超促排卵.然而,在临床上发现使用FSH进行卵巢刺激的不孕症患者其卵巢反应不一.FSH通过与卵泡刺激素受体(FSHR)结合介导其生理功能,目前在卵泡刺激素受体基因中发现超过900个SNP位点,其中一些SNP位点可能与FSH刺激引起的卵巢反应差异相关,在辅助生殖超促排卵过程中应该考虑这些SNPs对于卵巢功能的影响.通过预测疾病的遗传因素,为即将进行卵巢刺激的患者测定其基因多态性,以此制定个体化的卵巢刺激方案,达到优化不孕症治疗的临床目的.本文从遗传药理学角度,综述卵泡刺激素受体基因多态性对女性生殖功能的影响,探讨其临床意义.     

Oral exposure of Kunming mice to diisononyl phthalate induces hepatic and renal tissue injury through the accumulation of ROS. Protective effect of melatonin

Diisononyl phthalate (DINP) has been widely used in polyvinyl chloride (PVC) products and is ubiquitous as a substitute; however, its toxicity due to exposure remains to be determined. This study investigated the oxidative damage induced by DINP and the induced production of the pro-inflammation cytokines interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). Oral exposure to DINP induced oxidative damage and inflammatory responses in liver and kidney tissues through the accumulation of ROS, which may be an underlying mechanism for its toxicity. These changes may contribute to hepatic and renal histopathological alterations. Our data suggest that oxidative stress is involved in DINP-induced toxicity and that the co-administration of melatonin exerts a protective effect against DINP-induced toxicity.     

曼性低浓度吸入七氟醚对雌性小鼠受孕及胚胎的影响

目的探讨慢性低浓度吸入七氟醚对雌性小鼠受孕及胚胎的影响。方法选取6周龄雌性昆明小鼠60只,随机分为四组,每组各15只,对照组和七氟醚组,其中,七氟醚按吸入浓度分为30mg／L组、100mg／L组和300mg／L组;七氟醚组每天吸入对应浓度七氟醚6h,连续吸入4周,对照组吸入等量空气。然后将各组小鼠交配受孕后吸入同样浓度的七氟醚和空气至受孕19d时处死,检查各组受孕率、胚胎数及体重发育情况。结果300mg／L组受孕率低于对照组（P〈0．05）,各组畸形率、胎鼠数量差异无统计学意义（P〉O．05）,300mg／L组胎鼠平均体重低于对照组（P〈0．05）。结论慢性低浓度吸入〈100mg／L七氟醚对雌性小鼠受孕无影响．但当浓度〉300mg／L时可能对胎鼠生长有影响。     

Effects of dietary restriction on growth, neurobehavior, and reproduction in developing Kunmin mice.

The effects of dietary restriction (DR) on growth, neurobehavior, and reproduction in developing Kunmin mice were investigated in this study. Male and female mice were fed a standard rodent diet ad libitum (control), 80% of control (20% DR), or 65% of control (35% DR) for 3 months. Body weight of DR mice was reduced relative to control except that of females in the 20% DR group (no difference as compared with control group). Learning and memory retention test in a Y maze demonstrated that DR increased learning, but not retention, in male mice, whereas neither learning nor retention was affected in females. The open-field test revealed no difference in exploratory activity in all groups. Reproductive assessment showed that 35% DR retarded the maturation of reproductive function and reduced fertility compared with other groups. Furthermore, both 20% and 35% DR led to a lower level of sperm motility and a higher level of abnormal sperm relative to control mice. These findings indicate that DR does not cause damaging effects on growth and neurobehavior, but imposes a risk to reproductive development events.     

The effect of maternal exposure to di‐(2‐ethylhexyl)‐phthalate on fetal cardiac development in mice

Accumulating evidence has suggested a link between maternal di‐(2‐ethylhexyl)‐phthalate (DEHP) exposure and various developmental abnormalities. However, the evidence regarding the effect of maternal DEHP exposure on fetal cardiac development is scarce. The present study aimed to determine the effect of maternal DEHP exposure on fetal cardiac development in mice and explore the possible involved mechanism preliminarily. The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 250 mg kg^–1 DEHP group (n = 15), 500 mg kg^–1 DEHP group (n = 20) and 1 g kg^–1 DEHP group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from embryonic day (E)6.5 to E14.5. Maternal weights were monitored every day and samples were collected at E15.5. Hematoxylin and eosin staining was used to examine fetal cardiac malformations. Real‐time quantitative polymerase chain reaction and western blot were applied to detect peroxisome proliferator‐activated receptor (PPAR)α/PPARγ/Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. Maternal DEHP exposure significantly decreased maternal body weight, fetal weight and placental weight, and remarkably elevated fetal cardiac malformations rate. The phenotypes of cardiac anomalies mainly include septal defects, ventricular myocardium noncompaction and cardiac hypoplasia. Higher doses DEHP (500 mg kg^–1 and 1 g kg^–1) could significantly decreased fetal cardiac Gata4/Mef2c/Chf1 expression, while PPARγ expression was upregulated. Maternal exposure to higher doses of DEHP could result in fetal cardiac development malformations in mice and it might have resulted from the inhibition of cardiac GATA4/Mef2c/Chf1 expression via PPARγ activation.     

Effects of prepubertal exposure to xenoestrogen on development of estrogen target organs in female CD-1 mice

BACKGROUND: There have been no previous reports comparing the effects of prepubertal xenoestrogen exposure on development of the reproductive tract and mammary glands in female mice. The effects of genistein (GEN), resveratrol (RES), zearalenone (ZEA), zeranol (ZER), bisphenol A (BPA) and diethylstilbestrol (DES) were examined. MATERIALS AND METHODS: Beginning at 15 days of age, female CD-1 mice were administered 4 daily subcutaneous injections of 10 mg/kg/day of GEN, RES, ZEA, ZER or BPA, or 10 microg/kg/day of DES dissolved in dimethylsulfoxide (DMSO), or DMSO vehicle. Vaginal opening was checked; estrous cyclicity was monitored from 5, 9 or 21 weeks of age for 21 consecutive days; 6 animals per group were autopsied at 4, 8 and 24 weeks of age. RESULTS: Prepubertal exposure to GEN, ZEA, ZER and DES (but not RES or BPA) accelerated puberty onset (vaginal opening). Vaginal smears indicated that all xenoestrogen-treated mice were cycling, but ZEA-, ZER- and DES-treated mice spent more time in estrus. At 4 weeks of age, absence of corpora lutea (anovulatory ovary) was observed in the untreated controls (33%, 2/6) and the GEN (50%, 3/6), RES (50%, 3/6), ZEA (100%, 6/6), ZER (100%, 6/6), BPA (83%, 5/6) and DES groups (100%, 6/6). At 8 weeks of age, absence of corpora lutea was observed in the ZEA (33%, 2/6) group. Corpora lutea were present in all mice sacrificed at 24 weeks of age. Groups that received prepubertal xenoestrogen injections exhibited no morphological abnormalities of the uterus and vagina, and exhibited mammary gland growth similar to that of the untreated controls at all time-points. CONCLUSION: GEN, ZEA, ZER and DES (but not RES or BPA) caused early vaginal opening; mice exposed to ZEA, ZER or DES spent more time in the estrus phase; ZEA-treated mice had a longer period of anovulatory ovary than other xenoestrogen-treated mice; however, none of the xenoestrogens tested altered the uterine or vaginal morphology or mammary gland growth.     

Effects of in utero exposure to di-n-hexyl phthalate on the reproductive development of the male rat

Recently, the plasticizer di-n-hexyl phthalate (DnHP) has been demonstrated to be teratogenic and adversely affect the reproductive tract in male rat fetuses. This study was undertaken to determine the long-term effects of an in utero exposure to DnHP on the reproductive development of the male offspring. Di-2-ethylhexyl phthalate (DEHP), another phthalate ester known to disrupt the androgen-dependent sexual differentiation in the male rat, was used as a positive control. Pregnant Sprague-Dawley rats were administered DnHP or DEHP, by gavage on gestation Days 12–21, at doses of 0, 50, 125, 250, or 500 mg DnHP/kg-d and 500 mg DEHP/kg-d. DnHP had no significant effect on maternal body weight gain and pup weights during lactation. The proportion of live pups on postnatal day 1 was slightly, but not significantly, lower than control at 250 and 500 mg DnHP/kg-d. Male offspring displayed reduced anogenital distance on postnatal day 1 (PND) at 125 mg DnHP/kg-d and above, and areola/nipple retention before weaning and at adulthood at 250 and 500 mg DnHP/kg-d. At necropsy on PND 70–78 or PND 111–120, severe malformations of the reproductive tract were observed in young adult males at 125 mg DnHP/kg-d and higher doses. They mainly consisted of hypospadias, underdeveloped testis, and undescended testis. Additionally, histopathological examination revealed seminiferous tubule degeneration at the two high doses. Our results showed that prenatal exposure to DnHP caused permanent and dose-related alterations of the male rat reproductive development, with a similar profile as DEHP.     

Effects of lung exposure to carbon nanotubes on female fertility and pregnancy. A study in mice

We studied the effects of preconceptional exposure to multiwalled carbon nanotubes (MWCNTs): mature, female C57BL/6J mice were intratracheally instilled with 67 µg NM-400 MWCNT, and the following day co-housed with mature males, in breeding pairs. Time to delivery of the first litter, litter parameters, maternal inflammation and histopathology of lung and liver were recorded. In male offspring, locomotor activity, startle response, and daily sperm production (DSP) were assessed. In the dams, lung and liver bore evidence of MWCNT exposure when assessed 6 weeks and 4 months after exposure. A short delay in the delivery of the first litter was observed in exposed females. Litter parameters, behavior and DSP were similar in control and exposed groups. In conclusion, instillation of a single dose of MWCNT induced long lasting pathological changes in dam lung and liver. Theoretically, lung inflammation due to particle exposure could interfere with female reproductive parameters. Whether the observed lag in delivery of a first litter was in fact caused by exposure to MWCNT should be addressed in a study designed specifically to elucidate effects on the early processes involved in establishment of pregnancy. Exposure was not associated with changes in the assessed gestational or offspring parameters.